Leukemia is a cancer of the blood cells. Normally, blood cells are made in
an orderly, controlled way. When leukemia develops, the bone marrow produces
abnormal cells; therefore, the cells that are responsible for fighting
infections and preventing bleeding are not made correctly.
Leukemias are classified as acute or chronic; an acute leukemia progresses more rapidly. They are also classified by the type of white blood cells in which they arise -- lymphoid cells or myeloid cells. There are four primary types of leukemia:
Acute lymphocytic leukemia (ALL)
Acute myeloid leukemia (AML)
Chronic lymphocytic leukemia (CLL)
Chronic myelogenous leukemia (CML). The initial conventional treatment of CML includes spleen x-radiation and pharmaceutical drugs, mainly Busulfan and Hydroxyurea.
In addition, there are other forms that are rarer.
Diet and Leukemia, does food play a role?
Regular consumption of fruits and vegetables during the first two years of life is associated with a reduced risk of childhood leukemia. Children who regularly eat cured meats like bacon and hot dogs may have an increased risk of leukemia, while vegetables and soy products may help protect against cancer. Cured meats included foods like bacon, ham and hot dogs, as well as traditional Chinese staples like dried salted duck, salted fish and Chinese-style sausage. Most cured meats contain nitrites and nitrosamines. BMC Cancer, 2009.
Food Chemistry Toxicology. 2013. Polyphenols isolated from Allium cepa induces apoptosis by suppressing IAP-1 through inhibiting PI3K/Akt signaling pathways in human leukemic cells.
herbs for leukemia, over the counter products
Research regarding the use of supplements to prevent or treat leukemia is at its infancy, hence no confident statements can be made. My intent is to mention a few that have been studied.
Mangosteen herb has
potent compounds known as xanthones.
J Nat Products. 2003. Induction of apoptosis by xanthones from mangosteen in human leukemia cell lines. We examined the effects of six xanthones from the pericarps of mangosteen, Garcinia mangostana, on the cell growth inhibition of human leukemia cell line HL60. All xanthones displayed growth inhibitory effects, especially alpha-mangostin.
Antioxidants -- Children being treated for acute lymphoblastic leukemia seem more able to deal with their treatment if their levels of antioxidants don't drop too much. Kids with leukemia do not take enough antioxidants, which raises their risk of side effects during chemotherapy. Chemotherapy produces changes that stress the body's antioxidant defense system. Therefore, it's important that the diets of cancer patients contain adequate amounts of antioxidants. In a 6-month study, the researchers examined antioxidant intake and chemotherapy side effects in 103 children with acute lymphoblastic leukemia (ALL), the most common cancer in kids. During the study period subjects ingested vitamin E, total carotenoids, beta-carotene, and vitamin A in amounts that were 66, 30, 59, and 29 percent, respectively, of the US recommended dietary allowance. Greater intake of vitamin C was associated with fewer therapy delays, less side effects, and fewer days spent in the hospital. Similarly, the risk of infection and side effects decreased as vitamin E and beta-carotene intake increased.
Biomed Res Int. 2017. Cytotoxic Effect on Human Myeloma Cells and Leukemic Cells by the Agaricus blazei Based Mushroom Extract, Andosan.
Flavonoids found in vegetables
Bilberry has been studied
Curcumin could be of benefit.
Diindolylemethane also abbreviated as DIM.
Fucoidan has been studied regarding its effects on leukemia cells.
Indole-3-carbinol is found in cabbage, cauliflower, and Brussels sprouts.
Lycium berry is also known as wolfberry and goji berry.
Parthenolide, a compound found in feverfew, has been tested against chronic myelogenous leukemia.
Rosemary extracts have been found to be helpful.
Berberine in Coptis Chinensis herb
PLoS One. 2015. Paraptosis cell death induction by the thiamine analog benfotiamine in leukemia cells. We recently reported that oral benfotiamine induced a temporary but remarkable recovery from acute myeloid leukemia in an elderly patient who was ineligible for standard chemotherapy due to dementia and renal failure. In the present study we present evidences that benfotiamine possess antitumor activity against leukemia cells. In a panel of nine myeloid leukemia cell lines benfotiamine impaired the viability of HL-60, NB4, K562 and KG1 cells and also inhibited the growing of primary leukemic blasts. Our findings suggest that benfotiamine has antitumor therapeutic potential.
Cordyceps and leukemia
Cordyceps sinensis mycelium extract induces human premyelocytic leukemia cell apoptosis through mitochondrion pathway.
Exp Biol Med. 2007.
This study was to identify the signaling pathways for the induction of HL-60 cell apoptosis by Cordyceps sinensis mycelium extract. Cordyceps extract at 25 mug/ml induced nuclear fragmentation and DNA degradation, two hallmark events of apoptosis, in the HL-60 cells within 12-24 hrs of treatment.
Q. I suffer form
chronic myelogenous leukemia CML an I am doing well on Imatinib, known by the product name
Gleevec. Nevertheless I try to support my illness with some herbs and your site
which I came over just with recently is one of the best. My blood count shows
good results with a combination of feverfew, curcumin and black pepper. Recently
I learned about cordyceps mushroom and the good influence on leukemia Now I was
considering to start using this. According to a Chinese research team in can
boost up natural killer cells activity in leukemia patients to 400 percent.
According to a Sloan Kettering however cordyceps shows proliferation of
progenitor red blood cells and therefore should not be used in myelogeous
cancers. Being impressed with your expertise I would be very happy to know your
A. It is very difficult to extrapolate from in vitro lab studies to what would occur if a cordyceps supplement was taken orally. Also, the effects may be influenced by the type of cordyceps extract and the dosage used. There won't be easy answers until actual cordyceps studies are done in humans on different types of leukemia. Also, it is difficult to predict the influence of a cordyceps supplement when used in combination with medications and other supplements.
Q. I am a 68-year-old woman who was diagnosed with AML in March 2017 and I completed induction chemo and three rounds of consolidation. Since finishing chemo in July, I have been pursuing alternative treatments. I am in remission as evidence by bone marrow test in October. I am wanting to do natural approaches and I'm very interested in your article on feverfew. Since there seems to be very little downside, am wondering why not try taking it. The only prescription drug I take is acyclovir 400 mg 2x daily. I understand from your article that taking it in gradual doses initially is important and that 4 mgs was insufficient for blood saturation. Since AML is potentially a fast-growing cancer I want to do all that I can with natural treatments while I am in remission.
A. Although there have been some studies in the lab with parthenolide, an extract in feverfew, I am not aware of actual clinical trials in humans. Therefore, it is not easy to know how much to take, how long, and which brand is preferable.
Expert Opin Biol Ther. 2005. Feverfew: weeding out the root of leukemia. The compound parthenolide, which is derived from the medicinal plant feverfew, has recently been shown to preferentially induce AML stem cells to undergo apoptosis. Importantly, parthenolide had no discernable effect on normal blood cells. Thus, this naturally occurring agent may provide new avenues of investigation for the treatment of leukemia.
Cancer Invest. 2013. Inhibition of nuclear factor kappa B activation in early-stage chronic lymphocytic leukemia by omega-3 fatty acids. Department of Biochemistry and Microbiology, Marshall University School of Medicine, Huntington, WV, USA. Targeting the nuclear factor kappa B (NFκB) pathway is proposed as therapy for chronic lymphocytic leukemia (CLL). We hypothesized that an omega-3 fatty acids (n-3) supplement would suppress NFκB activation in lymphocytes of Rai Stage 0-1 CLL patients. The initial dose of 2.4 g n-3/day was gradually increased to 7.2 g n-3/day. After n-3 consumption: 1) plasma n-3 increased; 2) NFκB activation was suppressed in lymphocytes; 3) in vitro sensitivity of lymphocytes to doxorubicin was increased; and 4) expression of 32 genes in lymphocytes was significantly decreased.
Green Tea has EGCG
Doctors at the Mayo Clinic in Rochester, Minnesota, found that of four patients who started drinking green tea or taking green tea extracts, three showed clear improvements in their condition in the following months. The patients all had chronic lymphocytic leukemia, or CLL, a form of leukemia that usually arises during or after middle-age and typically progresses slowly. Like all types of leukemia, chronic lymphocytic leukemia is a cancer of the blood and bone marrow, in which abnormal white blood cells replace healthy blood cells. What's particularly interesting about these four cases, according to Dr. Tait Shanafelt, is that the patients all started using green tea on their own, after hearing media reports about a lab study Shanafelt and his colleagues conducted. That study showed that one compound found in green tea, known as EGCG, was able to kill cancer cells that were taken from chronic lymphocytic leukemia patients and put in a test tube with the tea compound. After the findings were published, the doctors became aware of four chronic lymphocytic leukemia patients at their center who had started using green tea products and seemed to be doing better. In interviewing the patients and reviewing their records, the doctors found that three showed signs of a regression in their cancer after they started to drink green tea or take green tea capsules. The fourth had an improvement in her white blood cell count, though her disease remained unchanged by standard criteria. In one case, the patient had been showing progressive swelling in her lymph nodes - one of the characteristics of chronic lymphocytic leukemia - before she starting taking green tea capsules twice a day. Over the next year, her lymph nodes steadily decreased in size. These cases alone cannot prove that green tea or its extracts conferred the benefits. An answer to that question, he said, awaits the outcome of an ongoing clinical trial he is leading. The study, sponsored by the National Cancer Institute, is testing the effects of a purified EGCG extract in treating chronic lymphocytic leukemia. Leukemia Research, online December 1, 2005.
Cause of Leukemia
There are many causes of leukemia, from exposure to toxins to viral infections and a consequence of prior chemotherapy for cancer.
Living near a fuel station may quadruple the risk of acute leukemia in children. French scientists who carried out a study of more than 500 infants found that a child whose home was near a fuel station or vehicle-repair garage was four times as likely to develop leukemia as a child whose home was further away. And the longer a child had lived nearby, the higher the risk of leukemia seemed to be. The prevalence of childhood leukemia is four in every 100,000 children, but it is the most common type of childhood cancer in developed countries. Few clear risk factors have been identified for the childhood variant, but exposure to benzene in the workplace has been identified as a possible factor in leukemia in adults and car pollution has a great deal of benzene. The risk appeared to be even greater for acute non-lymphoblastic leukemia, which was seven times more common among children living close to a fuel station or commercial garage. Occupational and Environmental Medicine, September 2004.
Power lines can cause a small increase in the risk of childhood leukemia. Other leukemia causes are radiation and benzene, and chemotherapeutic agents. People who spend years using older permanent hair dyes may have somewhat higher odds of developing leukemia.
Living near a high-voltage power line roughly doubles the risk of childhood cancers such as leukemia.
Women with early breast cancer who receive higher-than-standard doses of two chemotherapy drugs (epirubicin and cyclophosphamide) as "add-on" therapy are at increased risk of subsequently developing cancer of the blood. Although add-on therapy with these drugs for early breast cancer has increased the number of long-term survivors, a small risk of secondary acute myeloid leukemia (AML), with or without a pre-leukemia known as myelodysplastic syndrome (MDS), has been identified.
Greater body size significantly increases the risk of myeloid leukemia. Researchers studied data from a cohort of 40,909 adults who were followed for an average of 8.4 years. The incidence of myeloid leukemia was roughly five times higher among overweight and obese individuals than among individuals with normal or low weight. Specifically, the risk of myeloid leukemia increased 83 percent for every 10-kilogram increase in fat-free mass, and 35 percent per 10-centimeter increase in waist circumference.
Maternal infection with Helicobacter pylori -- the bacterium that causes most cases of stomach ulcers -- is associated with an increased risk of childhood leukemia in the offspring. Leukemia makes up 25 percent of all childhood cancers worldwide and so-called acute lymphoblastic leukemia (ALL), the most common form of the blood cancer, comprises about 80 percent of all childhood leukemias.
Exposure to pesticides in the womb or as a child can double the risk of developing acute leukemia. Children born to women who used insecticides in the home while pregnant and after the birth were nearly twice as likely as other youngsters to develop leukemia. Even insecticidal shampoos to kill head lice raised the odds of the disease.
A mother who contracts influenza, pneumonia, or a sexually transmitted disease around the time of pregnancy appears to be at increased risk of having a child that will develop leukemia.
Maternal Epstein-Barr virus (EBV) reactivation may be associated with a proportion of childhood leukemia. What that proportion this may be has yet to be defined.
Children who live close to an AM radio transmission tower may have an elevated risk of leukemia. American Journal of Epidemiology, August 1, 2007.
Morticians who use formaldehyde to embalm bodies have a higher risk of leukemia. In recent decades, more than 2 million U.S. workers have been exposed to formaldehyde, including anatomists, pathologists, and professionals who are employed in the funeral industry and who handle bodies or biological specimens preserved with formaldehyde.
Young children living near nuclear power plants have a significantly higher risk of developing leukemia and other forms of cancer.
Chemical exposure and chronic
An increased risk of chronic lymphoid leukemia occurs with benzene exposure. Two other oil-derived industrial chemicals, xylene and toluene, are also tied to greater chronic lymphoid leukemia risk. American Journal of Industrial Medicine, 2008.
The chances of children being diagnosed with leukemia seem to be related to the number of infections they had in their first year of life. Dr. Eve Roman from the University of York and colleagues identified 455 children with leukemia diagnosed between 2 and 5 years of age, and found that 425 of them had a type called acute lymphoblastic leukemia or ALL. Children diagnosed with ALL had significantly more infectious episodes in infancy than did a comparison group of matched "controls" without leukemia.
Pollution and leukemia
A University of Texas study found a possible link between childhood leukemia and living close to the city's refinery row along the Houston Ship Channel. Living within two miles of elevated levels of 1,3-butadiene around the ship channel's petrochemical complex was associated with an increased incidence of childhood acute lymphocytic leukemia compared with those living more than 10 miles away. The substance 1,3-butadiene is used to make petrochemicals like ethylene.
Common infections that affect mothers and babies may trigger certain types of childhood cancers. Leukemia and brain tumors, leading cancers in children, occur in clusters, which suggests that outbreaks of infections are a contributing cause of the disease. These infections could be minor, common illnesses...such a cold, mild flu or a respiratory infection. Leukemia is the most common childhood cancer, accounting for nearly one third of all cases. Most of the rise has been in children ages 1 to 4. An infection in the womb or early in life could lead to cancer in young people who carry mutant cells that would make them more vulnerable to the disease. The virus would hit this mutant cell and cause a second mutation, prompting the onset of cancers like leukemia or brain tumors.
Viruses and Leukemia
Viruses of the retrovirus and herpesvirus families may potentially cause certain human leukemias and lymphomas. The human T-cell leukemia virus type 1 causes adult T-cell leukemia. Influenza virus may also be a cause.
From 1974 to 2000, peaks in the rate of the acute lymphoblastic type of leukemia (ALL) among children in the UK seem to have occurred immediately after influenza epidemics. Perhaps some childhood leukemia may be triggered by infection occurring close to the time of diagnosis of leukemia. The findings are based on an analysis of data from the National Registry of Childhood Tumours, which covers the entire childhood population of the UK. During the 27-year period covered by the study, the rate of childhood ALL increased by 0.7 percent annually, on average. However, the rate spiked upward slightly in 1976 and 1990, just after influenza epidemics. Journal of the National Cancer Institute, March 15, 2006.
Patients on Gleevec for chronic myelogenous leukemia can develop severe congestive heart failure. See also lymphoma information. Leukemia may increase the risk for gout.
Feverfew: weeding out the root of leukaemia.
Expert Opin Biol Ther. 2005.
Malignant stem cells are central to the pathogenesis and perpetuation of acute myelogenous leukaemia (AML). Despite their crucial role, standard chemotherapy often does not target these critical cells and, thus, the 'root' of leukaemic disease is not eradicated. To derive better therapies, unique molecular features of malignant stem cells have been characterised for AML and evaluated with regard to ablation of disease. In the course of such studies, the compound parthenolide, which is derived from the medicinal plant feverfew, has recently been shown to preferentially induce AML stem cells to undergo apoptosis. Importantly, parthenolide had no discernable effect on normal blood cells. Thus, this naturally occurring agent may provide new avenues of investigation for the treatment of leukaemia. In this article, characteristics of parthenolide are reviewed.
The sesquiterpene lactone parthenolide induces apoptosis of human acute
myelogenous leukemia stem and progenitor cells.
The present studies demonstrate that parthenolide, a naturally-occurring small molecule, induces robust apoptosis in primary human acute myelogenous leukemia cells and blast crisis CML (bcCML) cells while sparing normal hematopoietic cells. Furthermore, analysis of progenitor cells using in vitro colony assays, as well as stem cells using the NOD/SCID xenograft model, show that parthenolide also preferentially targets acute myelogenous leukemia progenitor and stem cell populations. Notably, in comparison to the standard chemotherapy drug Ara-C, parthenolide is much more specific to leukemia cells. The molecular mechanism of parthenolide -mediated apoptosis is strongly associated with inhibition of NF-kappaB, pro-apoptotic activation of p53, and increased reactive oxygen species (ROS). Based on these findings, we propose that the activity of parthenolide triggers leukemia stem cells specific apoptosis, and as such represents a potentially important new class of drugs for leukemia stem cells targeted therapy.
Immunomodulation with interferon-gamma and granulocyte-colony-stimulating factor or granulocyte-macrophage colony-stimulating factor, helps deal with refractory fungal infections in patients with leukemia.
A child living near a high voltage power line may run a higher risk of contracting leukemia — the most common childhood cancer. But while there is an increased incidence of leukemia in children whose home address at birth was within 200 meters of a power line, the study’s authors admitted they had not proved that proximity to the power lines was the cause. “There is an association between childhood leukemia and proximity of home address at birth to high voltage power lines,” the study concluded.
Flavonoids induce apoptosis in human leukemia U937
cells through caspase- and caspase-calpain-dependent pathways.
Nutr Cancer. 2004.
Flavonoids are polyphenolic phytochemicals that are ubiquitous in plants and present in the common human diet. They may exert diverse beneficial effects, including antioxidant and anticarcinogenic activities. In this study we tested the apoptotic activity of 22 flavonoids and related compounds in leukemic U937 cells. Several flavones but none of the isoflavones or flavanones tested induced apoptotic cell death under these conditions. Regarding the mechanisms, galangin, luteolin, chrysin, and quercetin induced apoptosis in a way that required the activation of caspases 3 and 8, but not caspase 9. In contrast, an active role of calpains in addition to caspases was demonstrated in apoptosis induced by fisetin, apigenin, and 3,7-dihydroxyflavone. Our data show evidence of the proapoptotic properties of some flavonoids that could support their rational use as chemopreventive and therapeutic agents against carcinogenic disease.
Induction of apoptosis in cancer cells by Bilberry and the anthocyanins.
J Agric Food Chem. 2003..
Among ethanol extracts of 10 edible berries, bilberry extract was found to be the most effective at inhibiting the growth of HL60 human leukemia cells and HCT116 human colon carcinoma cells in vitro. Bilberry extract induced apoptotic cell bodies and nucleosomal DNA fragmentation in HL60 cells. The proportion of apoptotic cells induced by bilberry extract in HCT116 was much lower than that in HL60 cells, and DNA fragmentation was not induced in the former. Of the extracts tested, that from bilberry contained the largest amounts of phenolic compounds, including anthocyanins, and showed the greatest 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity. Pure delphinidin and malvidin, like the glycosides isolated from the bilberry extract, induced apoptosis in HL60 cells. These results indicate that the bilberry extract and the anthocyanins, bearing delphinidin or malvidin as the aglycon, inhibit the growth of HL60 cells through the induction of apoptosis. Only pure delphinidin and the glycoside isolated from the bilberry extract, but not malvidin and the glycoside, inhibited the growth of HCT116 cells.
Inhibition the growth of human leukemia cells by Lycium barbarum
polysaccharide ( wolfberry )
Wei Sheng Yan Jiu. 2001.
The effect and the mechanism of Wolfberry polysaccharide on inhibiting the growth of human leukemia HL-60 cells were examined. Wolfberry could inhibit the growth of HL-60 cells in dose-dependent manner and decrease the membrane fluidity of the cell. Agarose gel electrophoresis of DNA from the cells treated with wolfberry revealed a "DNA ladder" and positive TUNEL test. The results showed that the apoptosis of HL-60 cells induced by wolberry maybe its important mechanism on anti-tumorgenesis.
Children who attend daycare regularly in the first few months of life are less likely to develop acute lymphoblastic leukemia, the most common form of the blood cancer, than kids who do not. The most plausible explanation for why daycare seems to protect against leukemia is that it allows children to be exposed to common infections early in life.
Cytotoxic effects of Coptis chinensis and Epimedium sagittatum extracts
and their major constituents (berberine, coptisine and icariin) on hepatoma and
leukemia cell growth.
Clin Exp Pharmacol Physiol. 2004.
The results of the present study suggest that the Coptis chinensis extract and its major constituents berberine and coptisine possess active antihepatoma and anti leukemia activities.
If left untreated,
polycythemia vera can
develop into leukemia.
Catha edulis (Khat) induces cell death by apoptosis in leukemia cell lines.
Natural leukemia treatment questions
Q. I read your article about how parthenolide might be good for Leukemia patients. Do you know if they still have any clinical trials on this?? Also, would it help if I took supplements of parthenolide or is that a waste?? I have AML and am not doing well at all. I have tried bmt and all other treatments basically.
A. Unfortunately, so little research has been done with natural herbs and supplements for leukemia treatment that it is very difficult to give any suggestions with any certainty. Please discuss with your health care provider the information on this leukemia page and then decide on a course of action.
Q. Your webpage on leukemia states that leukemia will
increase the risk of gout. Why is this so?
A. Leukemia leads to high uric acid levels which make one more prone to gout.
Q. I was diagnosed with Acute Myeloid Leukemia in 2004
- after much chemo went in remission and the cancer returned in 2006 - given
much chemo. and was told I had a few days to live on 8/19/06. Discovered
glyconutrients, Essaic, Acai berry - cancer returned 5/07 I receive transfusions
as needed twice a week now. Fucoidan sounds promising could you provide any
information on this please? I am 57.
A. We wish you optimal healing and keep your strength. Please see fucoidan for info.
Q. What advice can you offer regarding: B-cell, chronic
lymphocytic leukemia and chronic bronchitis? For instance, would fulvic acid be
A. We have not studied the role of fulvic acid in leukemia.
Q. Last week I was diagnosed by my primary physician of
having leukemia. My white blood cell count was 3 times higher than 3 month ago.
I was sent immediately to a blood oncologist and he confirmed the high white
blood cell count. He took some bone marrow from my hipbone and this coming week
I will have the results of those tests.
I ate a lot of soy products in my life and my age is 78 years. I am in very good condition except my bones are starting to hurt and I am getting tired more easily. Would genistein supplements help?
A. We have not seen any human studies using genistein for leukemia treatment. We wish you optimal healing. These are difficult times for you.
Q. My 36 year old daughter has Chronic Lymphocytic
Leukemia, Type1, Stage 4. They are "Watchful Waiting" meaning they are wasting
precious time doing nothing other than testing her blood monthly till it gets
high enough to give her chemo. It's now at 36, so it will be sooner than the 3
years that had projected for her. I am desperately trying to find something that
will stabilize her white blood count even if it just postpones the chemo
treatment for another year because by then there could be a cure, Please help if
you can. It's very sad for her since she also has a 2 and 3 year old.
A. I hope you are able to review the information on this page regarding natural supplements with her doctor.
Q. I am 75 yo active female that was diagnosed with AML
leukemia in 2017. I tolerated induction therapy and two rounds of HiDAC therapy.
I still have an abnormal chromosome and two mutations. I start Dacogen next week
for one year. Unsure what happens after that. I take a multitude of supplements
to build up my immune system. I am taking a mushroom supplement, beta glucan,
honokiol magnolia bark along with pectasol-C MCP, green tea, Vit C, D, selenium,
resveratrol, curcumin, CQ10, vit B complex. What do I stop that interferes with
chemo. My oncologist won't let me take anything but vitamins C and D.
A. Each person is different and it is quite complicated to determine for each person which supplements or herbal remedies help with chemo or hurt with chemo. It may be a good idea to take a break from supplementation during medical treatment.
Q. Hi, I am from Team In Training, and we are trying to raise awareness for Leukemia and Lymphoma and I was wondering if you could post our website URL on your link website. Our URL is teamintraining dot org/cpa. Kevin Johnson, Team In Training.
Q. I am wondering if there are specific supplements for a
cure for CML Leukemia? Currently I am on a break from my Tasignia because of
toxicity. I am trying to cure my Leukemia myself as I do not want to go back on
the drug that will eventually kill me one day. I have tried a few things that
have not worked. Currently I am on the Budwig diet, 300 mg reversatrol, high
doses of curcumin, mushroom blend and alpha lypolic acid.It is really difficult
to find information on success stories.
A. There is very little information or human studies on natural ways to reduce the risk of leukemia or to treat it once it occurs.